Microparticulate Systems for the Delivery of Proteins and Vaccines

544 Pages·1996·19.052 MB·\544

by  Smadar Cohen (Editor), Howard Bernstein (Editor)

Microparticulate Systems
for flie Delivery of
Proteins and iteccines
DRUGS AND THE PHARMACEUTICAL SCIENCES
James Swarbrick, Executive Editor
AAI, Inc.
Wilmington, North Carolina
Advisory Board
Larry L. Augsburger David E. Nichols
University of Maryland Purdue University
Baltimore, Maryland West Lafayette, Indiana
Douwe D. Breimer Stephen G. Schulman
Gorlaeus Laboratories University of Florida
Leiden, The Netherlands Gainesville, Florida
Trevor M. Jones Jerome P. Skelly
The Association of the Copley Pharmaceutical, Inc.
British Pharmaceutical Industry Canton, Massachusetts
London, United Kingdom
Hans E. Junginger Felix Theeuwes
Leiden/Amsterdam Center Alza Corporation
for Drug Research Palo Alto, California
Leiden, The Netherlands
Vincent H. L. Lee Geoffrey T. Tucker
University of Southern California University of Sheffield
Los Angeles, California Royal Hallamshire Hospital
Sheffield, United Kingdom
Peter G. Welling
Parke-Davis, Inc.
Ann Arbor, Michigan
DRUGS AND THE PHARMACEUTICAL SCIENCES
A Series of Textbooks and Monographs
edited by
James Swarbrick
AAi, Inc.
Wilmington, North Carolina
1. Pharmacokinetics, Miio Giba/di and Donald Perrier
2. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Sidney H. Willig, Murray M. Tuckerman, and William
S. Hitchings IV
3. Microencapsulation, edited by J. R. Nixon
4. Drug Metabolism: Chemical and Biochemical Aspects, Bernard Testa
and Peter Jenner
5. New Drugs: Discovery and Development, edited by A/an A. Rubin
6. Sustained and Controlled Release Drug Delivery Systems, edited by
Joseph R. Robinson
7. Modern Pharmaceutics, edited by Gilbert S. Banker and Christopher
T. Rhodes
8. Prescription Drugs in Short Supply: Case Histories, Michael A.
Schwartz
9. Activated Charcoal: Antidotal and Other Medical Uses, David 0.
Cooney
10. Concepts in Drug Metabolism (in two parts), edited by Peter Jenner
and Bernard Testa
11. Pharmaceutical Analysis: Modern Methods (in two parts), edited by
James W. Munson
1 2. Techniques of Solubilization of Drugs, edited by Samuel H. Yalkow-
sky
13. Orphan Drugs, edited by Fred E Karch
14. Novel Drug Delivery Systems: Fundamentals, Developmental Con­
cepts, Biomedical Assessments, Yie W. Chien
15. Pharmacokinetics: Second Edition, Revised and Expanded, Milo
Gibaldi and Donald Perrier
1 6. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Second Edition, Revised and Expanded, Sidney H.
Willig, Murray M. Tuckerman, and William S. Hitchings IV
17. Formulation of Veterinary Dosage Forms, edited by Jack Blodinger
18. Dermatological Formulations: Percutaneous Absorption, Brian W.
Barry
19. The Clinical Research Process in the Pharmaceutical Industry, edited
by Gary M. Matoren
20. Microencapsulation and Related Drug Processes, Patrick B. Deasy
21. Drugs and Nutrients: The Interactive Effects, edited by Daphne A.
Roe and T. Colin Campbell
22. Biotechnology of Industrial Antibiotics, Erick J. Vandamme
23. Pharmaceutical Process Validation, edited by Bernard T. Loftus and
Robert A. Nash
24. Anticancer and Interferon Agents: Synthesis and Properties, edited by
Raphael M. Ottenbrite and George B. Butler
25. Pharmaceutical Statistics: Practical and Clinical Applications, Sanford
Bolton
26. Drug Dynamics for Analytical, Clinical, and Biological Chemists,
Benjamin J. Gudzinowicz, Burrows T. Younkin, Jr., and Michael J.
Gudzinowicz
27. Modern Analysis of Antibiotics, edited by Adjoran Aszalos
28. Solubility and Related Properties, Kenneth C. James
29. Controlled Drug Delivery: Fundamentals and Applications, Second Edi­
tion, Revised and Expanded, edited by Joseph R. Robinson and
Vincent H. Lee
30. New Drug Approval Process: Clinical and Regulatory Management,
edited by Richard A. Guarino
31. Transdermal Controlled Systemic Medications, edited by Yie W. Chien
32. Drug Delivery Devices: Fundamentals and Applications, edited by
Praveen Ty/e
33. Pharmacokinetics: Regulatory • Industrial • Academic Perspectives,
edited by Peter G. Welling and Francis L. S. Tse
34. Clinical Drug Trials and Tribulations, edited by Alien E. Cato
35. Transdermal Drug Delivery: Developmental Issues and Research Ini­
tiatives, edited by Jonathan Hadgraft and Richard H. Guy
36. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, edi­
ted by James W. McGinity
37. Pharmaceutical Pelletization Technology, edited by Isaac Ghebre-
Se/lassie
38. Good Laboratory Practice Regulations, edited by Alien F. Hirsch
39. Nasal Systemic Drug Delivery, Yie W. Chien, Kenneth S. E. Su, and
Shyi-Feu Chang
40. Modern Pharmaceutics: Second Edition, Revised and Expanded,
edited by Gilbert S. Banker and Christopher T. Rhodes
41. Specialized Drug Delivery Systems: Manufacturing and Production
Technology, edited by Praveen Ty/e
42. Topical Drug Delivery Formulations, edited by David W. Osborne and
Anton FI. Amann
43. Drug Stability: Principles and Practices, Jens T. Carstensen
44. Pharmaceutical Statistics: Practical and Clinical Applications, Second
Edition, Revised and Expanded, Sanford Bolton
45. Biodegradable Polymers as Drug Delivery Systems, edited by Mark
Chasin and Robert Langer
46. Preclinical Drug Disposition: A Laboratory Handbook, Francis L. S.
Tse and James J. Jaffe
47. HPLC in the Pharmaceutical Industry, edited by Godwin W. Fong and
Stanley K. Lam
48. Pharmaceutical Bioequivalence, edited by Peter G. Welling, Francis L.
S. Tse, and Shrikant V. Dinghe
49. Pharmaceutical Dissolution Testing, Umesh V. Banakar
50. Novel Drug Delivery Systems: Second Edition, Revised and Expanded,
Yie W. Ch ien
51. Managing the Clinical Drug Development Process, David M. Coc-
chetto and Ronald V. Nardi
52. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Third Edition, edited by Sidney H. Wil/ig and James
R. Stoker
53. Prodrugs: Topical and Ocular Drug Delivery, edited by Kenneth B.
Sloan
54. Pharmaceutical Inhalation Aerosol Technology, edited by Anthony J.
Hickey
55. Radiopharmaceuticals: Chemistry and Pharmacology, edited by Adrian
D. Nunn
56. New Drug Approval Process: Second Edition, Revised and Expanded,
edited by Richard A. Guarino
57. Pharmaceutical Process Validation: Second Edition, Revised and Ex­
panded, edited by Ira R. Berry and Robert A. Nash
58. Ophthalmic Drug Delivery Systems, edited by Ashim K. Mitra
59. Pharmaceutical Skin Penetration Enhancement, edited by Kenneth A.
Walters and Jonathan Hadgraft
60. Colonic Drug Absorption and Metabolism, edited by Peter R. Bieck
61 .^Pharmaceutical Particulate Carriers: Therapeutic Applications, edited
by Alain Rolland
62. Drug Permeation Enhancement: Theory and Applications, edited by
Dean S. Hsieh
63. Glycopeptide Antibiotics, edited by Ramakrishnan Nagarajan
64. Achieving Sterility in Medical and Pharmaceutical Products, Nigel A.
Halls
65. Multiparticulate Oral Drug Delivery, edited by Isaac Ghebre-Se/lassie
66. Colloidal Drug Delivery Systems, edited by Jorg Kreuter
67. Pharmacokinetics: Regulatory • Industrial • Academic Perspectives,
Second Edition, edited by Peter G. Welling and Francis L. S. Tse
68. Drug Stability: Principles and Practices, Second Edition, Revised and
Expanded, Jens T. Carstensen
69. Good Laboratory Practice Regulations: Second Edition, Revised and
Expanded, edited by Sandy Weinberg
70. Physical Characterization of Pharmaceutical Solids, edited by Harry G.
Brittain
71. Pharmaceutical Powder Compaction Technology, edited by Goran
Alderborn and Christer Nystrom
72. Modern Pharmaceutics: Third Edition, Revised and Expanded, edited
by Gilbert S. Banker and Christopher T. Rhodes
73. Microencapsulation: Methods and Industrial Applications, edited by
Simon Benita
74. Oral Mucosal Drug Delivery, edited by Michael J. Rath bone
75. Clinical Research in Pharmaceutical Development, edited by Barry Bleidt
and Michael Montagne
76. The Drug Development Process: Increasing Efficiency and Cost-
Effectiveness, edited by Peter G. Welling, Louis Lasagna, and Umesh
V. Banakar
77. Microparticulate Systems for the Delivery of Proteins and Vaccines,
edited by Smadar Cohen and Howard Bernstein
78. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Fourth Edition, Revised and Expanded, Sidney H.
Willig and James R. Stoker
ADDITIONAL VOLUMES IN PREPARATION
Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms: Second
Edition, edited by James W. McGinity
Pharmaceutical Statistics: Practical and Clinical Applications, Third
Edition, Sanford Bolton
Mcroparticulate Systems
for the Delivery ol
Proteins and Vaccines
edited by
Smadar Cohen
Ben-Gurion University of the Negev
Beer-Sheva, Israel
Howard Bernstein
Acusphere, Inc.
Cambridge, Massachusetts
CRC Press
Taylor & Francis Group
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
Library of Congress Cataloging-in-Publication Data
Microparticulate systems for the delivery of proteins and vaccines / edited by
Smadar Cohen, Howard Bernstein.
p. cm. — (Drugs and the pharmaceutical sciences, v. 77)
Includes index.
ISBN 0-8247-9753-1 (hardcover : alk. paper)
1. Microencapsulation. 2. Protein drugs—Controlled release. 3. Vaccines
—Controlled release. I. Cohen, Smadar. II. Bernstein, Howard. III. Series.
RS201.C3M544 1996
615'. 6—dc20 96-25983
CIP
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Current printing (last digit):
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Preface
There are multiple FDA-approved protein therapeutic agents and many more in
various stages of preclinical and clinical development. For these molecules to
realize their full therapeutic potential, improved ways of delivering these drugs
must be developed. Almost 20 years have passed since the initial demonstration
that macromolecules, such as proteins, can be delivered at controlled rates from
polymeric matrices. Since then, we have witnessed the development of numer­
ous encapsulation techniques and microparticulate-delivery systems using both
natural and synthetic polymers. The systems, to date, have been developed
almost exclusively for conventional, low molecular weight drugs and peptides.
As we look ahead toward advances in protein delivery, the areas of greatest
consequence will be understanding and developing ways to stabilize these mol­
ecules, both during the microencapsulation processes and while encapsulated
within the delivery system. This book offers a review of the recent advances
made in developing microparticulate systems for the delivery of therapeutic
proteins and vaccines.
The book begins with an account on protein stability issues as related to
encapsulation and controlled delivery from biodegradable polymer micro­
spheres. Chapters 2-5 present various methods of protein microencapsulation,
including new approaches that do not involve organic solvents, such as super­
critical fluids (Chapter 3), ionic cross-linking of the hydrogel-like polyphos-
phazenes (Chapter 4), and liposphere technology (Chapter 5). In Chapter 6,
various spectral and microscopic methods are applied to microsphere character­
ization.
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